Gemcitabine Hydrochloride and Alvocidib in Treating Patients With Solid Tumors

Phase 1

Completed

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Interventions: Drug: gemcitabine hydrochloride
Drug: alvocidib
Other: pharmacological study

Registration Number: NCT00072436

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase I trial is studying the side effects and best dose of gemcitabine hydrochloride and alvocidib in treating patients with solid tumors. Drugs used in chemotherapy, such as gemcitabine hydrochloride and alvocidib, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

Detailed Description: PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of gemcitabine and flavopiridol in patients with solid tumors.

SECONDARY OBJECTIVES:

I. Determine the safety profile and toxic effects of this regimen in these patients.

II. Determine the pharmacokinetics of flavopiridol with and without gemcitabine in these patients.

III. Determine, using pharmacodynamic assays, the activity of flavopiridol as a cdk inhibitor in these patients.

IV. Determine, using pharmacodynamic assays, the markers of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and alvocidib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.

Patients are followed at 30 days after study completion.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 58

Inclusion Criteria

Negative pregnancy test
Fertile patients must use effective contraception
No active infection
No severe malnutrition
No more than 2 prior chemotherapy regimens:
- Prior combined modality therapy (e.g., full-dose chemotherapy with radiosensitizing chemotherapy and radiotherapy) is considered 1 prior regimen if all therapy was delivered as part of 1 comprehensive treatment plan
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No other concurrent chemotherapy
At least 6 months since prior radiotherapy to the lung parenchyma or mediastinum and no evidence of radiation pneumonitis on chest CT scan
At least 4 weeks since other prior radiotherapy and recovered
No prior radiotherapy to more than 50% of marrow volume
No concurrent radiotherapy
Histologically confirmed solid tumor for which gemcitabine is a treatment option OR for which no efficacious therapy exists
Must meet criteria for 1 of the following:
- Measurable disease:
  - At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- Nonmeasurable disease, including any of the following:
  - Small lesions (less than 20 mm by conventional techniques OR less than 10 mm by spiral CT scan)
  - Bone lesions
  - Cytologically positive pleural or peritoneal disease
  - Elevated tumor markers (e.g., carcinoembryonic antigen, CA 125, CA 19-9, or other tumor marker)
  - Multinodular or confluent nonmeasurable pulmonary, hepatic, adrenal, intra-abdominal, or skin metastases
  - No active CNS metastases
  - Previously treated CNS metastases must be stable with no symptoms for 4 weeks after completion of treatment AND patient must be off steroid therapy or on a stable dose for at least the past 2 weeks
  - No known leptomeningeal metastases
Performance status:
- ECOG 0-1
Hematopoietic:
- Absolute neutrophil count at least 1,500/mm3;
- Platelet count at least 100,000/mm3
Hepatic:
- Bilirubin no greater than 1.5 mg/dL;
- SGOT no greater than 2.5 times upper limit of normal
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 50 mL/min
Cardiovascular:
- None of the following within the past 6 months:
  - Myocardial infarction;
  - Unstable angina;
  - Transient ischemic attack;
  - Cerebrovascular accident
    - No new cardiac arrhythmia possibly related to cardiac ischemia;
    - No large and potentially symptomatic pericardial effusion;
    - No cardiac disease that would preclude study participation
Pulmonary:
- No pulmonary embolism within the past 6 months;
- No large and potentially symptomatic pleural effusion;
- No pulmonary disease that would preclude study participation
Gastrointestinal:
- No intractable emesis;
- No grade 2 or greater chronic diarrheal disease within the past 6 months
Not pregnant or nursing

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	gemcitabine hydrochloride	Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and alvocidib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.
Treatment	pharmacological study	Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and alvocidib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.
Treatment	alvocidib	Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and alvocidib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT) graded by National Cancer Institute (NCI) Common Toxicity Criteria	28 days
Maximum tolerated dose, defined as one dose level below the dose that induces DLT in more than 1/6 patients	28 days

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (3): Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States

Gemcitabine Hydrochloride and Alvocidib in Treating Patients With Solid Tumors

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts